Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer

Joseph A. Sparano, Lori J. Goldstein, Barrett H. Childs, Steven Shak, Diana Brassard, Sunil Badve, Frederick L. Baehner, Roberto Bugarini, Steve Rowley, Edith A. Perez, Lawrence N. Shulman, Silvana Martino, Nancy E. Davidson, Paraic A. Kenny, George W. Sledge, Robert Gray

Research output: Contribution to journalArticle

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Abstract

Purpose: To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results: Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8-14.1] in the low and 20.4% (95% CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions: GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.

Original languageEnglish
Pages (from-to)7194-7203
Number of pages10
JournalClinical Cancer Research
Volume17
Issue number22
DOIs
StatePublished - Nov 15 2011

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GRB7 Adaptor Protein
Triple Negative Breast Neoplasms
Anthracyclines
Adjuvant Chemotherapy
RNA
Recurrence
Doxorubicin
Proportional Hazards Models
Confidence Intervals
Gene Expression
Drug Therapy
Therapeutics
Reverse Transcriptase Polymerase Chain Reaction
Genes
Research Design
Biomarkers

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer. / Sparano, Joseph A.; Goldstein, Lori J.; Childs, Barrett H.; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L.; Bugarini, Roberto; Rowley, Steve; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Davidson, Nancy E.; Kenny, Paraic A.; Sledge, George W.; Gray, Robert.

In: Clinical Cancer Research, Vol. 17, No. 22, 15.11.2011, p. 7194-7203.

Research output: Contribution to journalArticle

Sparano, JA, Goldstein, LJ, Childs, BH, Shak, S, Brassard, D, Badve, S, Baehner, FL, Bugarini, R, Rowley, S, Perez, EA, Shulman, LN, Martino, S, Davidson, NE, Kenny, PA, Sledge, GW & Gray, R 2011, 'Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer', Clinical Cancer Research, vol. 17, no. 22, pp. 7194-7203. https://doi.org/10.1158/1078-0432.CCR-10-3357
Sparano, Joseph A. ; Goldstein, Lori J. ; Childs, Barrett H. ; Shak, Steven ; Brassard, Diana ; Badve, Sunil ; Baehner, Frederick L. ; Bugarini, Roberto ; Rowley, Steve ; Perez, Edith A. ; Shulman, Lawrence N. ; Martino, Silvana ; Davidson, Nancy E. ; Kenny, Paraic A. ; Sledge, George W. ; Gray, Robert. / Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 22. pp. 7194-7203.
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abstract = "Purpose: To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results: Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5{\%} [95{\%} confidence intervals (CI), 7.8-14.1] in the low and 20.4{\%} (95{\%} CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions: GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.",
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T1 - Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer

AU - Sparano, Joseph A.

AU - Goldstein, Lori J.

AU - Childs, Barrett H.

AU - Shak, Steven

AU - Brassard, Diana

AU - Badve, Sunil

AU - Baehner, Frederick L.

AU - Bugarini, Roberto

AU - Rowley, Steve

AU - Perez, Edith A.

AU - Shulman, Lawrence N.

AU - Martino, Silvana

AU - Davidson, Nancy E.

AU - Kenny, Paraic A.

AU - Sledge, George W.

AU - Gray, Robert

PY - 2011/11/15

Y1 - 2011/11/15

N2 - Purpose: To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results: Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8-14.1] in the low and 20.4% (95% CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions: GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.

AB - Purpose: To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results: Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8-14.1] in the low and 20.4% (95% CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions: GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.

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